{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:55:25Z","timestamp":1793332525188,"version":"4.5.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T00:00:00Z","timestamp":1539648000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T00:00:00Z","timestamp":1539648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["F15-04283"],"award-info":[{"award-number":["F15-04283"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U34AG051425-0"],"award-info":[{"award-number":["U34AG051425-0"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BC Lung Association, MITACS and the Michael Smith Foundation for Health Research"},{"name":"Canada Research Chairs (CA) in Occupational and Environmental Lung Disease"},{"name":"Canada Research Chairs (CA) in Social Epigenetics"},{"name":"Senior Fellow of the Canadian Institute for Advanced Research"},{"name":"Sunny Hill BC Leadership Chair in Child Development"},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["281297"],"award-info":[{"award-number":["281297"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Epigenet"],"published-print":{"date-parts":[[2018,12]]},"DOI":"10.1186\/s13148-018-0556-2","type":"journal-article","created":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T13:46:04Z","timestamp":1539697564000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":147,"title":["Systematic evaluation of DNA methylation age estimation with common preprocessing methods and the Infinium MethylationEPIC BeadChip array"],"prefix":"10.1186","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0500-9173","authenticated-orcid":false,"given":"Lisa M","family":"McEwen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meaghan J","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Tse Shen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel D","family":"Edgar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas T","family":"Husquin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia L","family":"MacIsaac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia E","family":"Ramadori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander M","family":"Morin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher F","family":"Rider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Carlsten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Llu\u00eds","family":"Quintana-Murci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Horvath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S","family":"Kobor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,10,16]]},"reference":[{"issue":"10","key":"556_CR1","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1093\/bioinformatics\/btu049","volume":"30","author":"MJ Aryee","year":"2014","unstructured":"Aryee MJ, et al. Minfi: a flexible and comprehensive bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics. 2014;30(10):1363\u20139.","journal-title":"Bioinformatics"},{"issue":"1","key":"556_CR2","doi-asserted-by":"publisher","first-page":"177","DOI":"10.2217\/epi.09.14","volume":"1","author":"M Bibikova","year":"2009","unstructured":"Bibikova M, et al. Genome-wide DNA methylation profiling using Infinium\u00ae assay. Epigenomics. 2009;1(1):177\u2013200.","journal-title":"Epigenomics"},{"issue":"6","key":"556_CR3","doi-asserted-by":"publisher","first-page":"e14821","DOI":"10.1371\/journal.pone.0014821","volume":"6","author":"S Bocklandt","year":"2011","unstructured":"Bocklandt S, et al. Epigenetic predictor of age. PloS one. 2011;6(6):e14821.","journal-title":"PloS one"},{"issue":"1","key":"556_CR4","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s13148-016-0186-5","volume":"8","author":"LP Breitling","year":"2016","unstructured":"Breitling LP, et al. Frailty is associated with the epigenetic clock but not with telomere length in a German cohort. Clin Epigenetics. 2016;8(1):21.","journal-title":"Clin Epigenetics"},{"key":"556_CR5","unstructured":"Davis S, Du P, Bilke S, Triche, Jr. T, Bootwalla M. methylumi: Handle Illumina methylation data. R package version 2.26.0; 2017."},{"issue":"6","key":"556_CR6","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1093\/bib\/bbt054","volume":"15","author":"S Dedeurwaerder","year":"2014","unstructured":"Dedeurwaerder S, et al. A comprehensive overview of Infinium HumanMethylation450 data processing. Brief Bioinform. 2014;15(6):929\u201341.","journal-title":"Brief Bioinform"},{"issue":"1","key":"556_CR7","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s13072-015-0011-y","volume":"8","author":"P Farr\u00e9","year":"2015","unstructured":"Farr\u00e9 P, et al. Concordant and discordant DNA methylation signatures of aging in human blood and brain. Epigenetics Chromatin. 2015;8(1):19.","journal-title":"Epigenetics Chromatin"},{"key":"556_CR8","doi-asserted-by":"crossref","unstructured":"Fortin JP, Triche TJ Jr, Hansen KD. Preprocessing, normalization and integration of the Illumina HumanMethylationEPIC array with minfi. Bioinformatics. 2016.","DOI":"10.1101\/065490"},{"issue":"6","key":"556_CR9","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1111\/acel.12005","volume":"11","author":"P Garagnani","year":"2012","unstructured":"Garagnani P, et al. Methylation of ELOVL2 gene as a new epigenetic marker of age. Aging Cell. 2012;11(6):1132\u20134.","journal-title":"Aging Cell"},{"issue":"2","key":"556_CR10","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.molcel.2012.10.016","volume":"49","author":"G Hannum","year":"2013","unstructured":"Hannum G, et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell. 2013;49(2):359\u201367.","journal-title":"Mol Cell"},{"issue":"1","key":"556_CR11","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s13059-015-0679-0","volume":"16","author":"SC Hicks","year":"2015","unstructured":"Hicks SC, Irizarry RA. Quantro: a data-driven approach to guide the choice of an appropriate normalization method. Genome Biol. 2015;16(1):117.","journal-title":"Genome Biol"},{"issue":"10","key":"556_CR12","doi-asserted-by":"publisher","first-page":"R115","DOI":"10.1186\/gb-2013-14-10-r115","volume":"14","author":"S Horvath","year":"2013","unstructured":"Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14(10):R115.","journal-title":"Genome Biol"},{"issue":"10","key":"556_CR13","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1093\/infdis\/jiv277","volume":"212","author":"S Horvath","year":"2015","unstructured":"Horvath S, Levine AJ. HIV-1 infection accelerates age according to the epigenetic clock. J Infect Dis. 2015;212(10):1563\u201373.","journal-title":"J Infect Dis"},{"key":"556_CR14","first-page":"223","volume":"23","author":"S Horvath","year":"2018","unstructured":"Horvath S, Raj K. DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genetics. 2018;23:223.","journal-title":"Nat Rev Genetics"},{"key":"556_CR15","doi-asserted-by":"crossref","unstructured":"Horvath S, Ritz BR. Increased epigenetic age and granulocyte counts in the blood of Parkinson's disease patients. Aging. 2015.","DOI":"10.18632\/aging.100859"},{"issue":"10","key":"556_CR16","doi-asserted-by":"publisher","first-page":"R97","DOI":"10.1186\/gb-2012-13-10-r97","volume":"13","author":"S Horvath","year":"2012","unstructured":"Horvath S, et al. Aging effects on DNA methylation modules in human brain and blood tissue. Genome Biol. 2012;13(10):R97.","journal-title":"Genome Biol"},{"issue":"1","key":"556_CR17","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1186\/s13059-016-1030-0","volume":"17","author":"S Horvath","year":"2016","unstructured":"Horvath S, et al. An epigenetic clock analysis of race\/ethnicity, sex, and coronary heart disease. Genome Biol. 2016;17(1):171.","journal-title":"Genome Biol"},{"key":"556_CR18","doi-asserted-by":"crossref","unstructured":"Horvath S, et al. Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring. Aging. 2015.","DOI":"10.18632\/aging.100861"},{"key":"556_CR19","doi-asserted-by":"crossref","unstructured":"Husquin LT, et al. Exploring the genetic basis of human population differences in DNA methylation and their causal impact on immune gene regulation. bioRxiv. 2018:371872.","DOI":"10.1101\/371872"},{"issue":"5532","key":"556_CR20","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1126\/science.1063852","volume":"293","author":"PA Jones","year":"2001","unstructured":"Jones PA, Takai D. The role of DNA methylation in mammalian epigenetics. Science (New York, NY). 2001;293(5532):1068\u201370.","journal-title":"Science (New York, NY)"},{"issue":"11","key":"556_CR21","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.2217\/epi-2017-0078","volume":"9","author":"MW Logue","year":"2017","unstructured":"Logue MW, et al. The correlation of methylation levels measured using Illumina 450K and EPIC BeadChips in blood samples. Epigenomics. 2017;9(11):1363\u201371.","journal-title":"Epigenomics"},{"issue":"1","key":"556_CR22","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s13059-015-0584-6","volume":"16","author":"RE Marioni","year":"2015","unstructured":"Marioni RE, Shah S, McRae AF, Chen BH, et al. DNA methylation age of blood predicts all-cause mortality in later life. Genome Biol. 2015a;16(1):25.","journal-title":"Genome Biol"},{"issue":"4","key":"556_CR23","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1093\/ije\/dyu277","volume":"44","author":"Riccardo E Marioni","year":"2015","unstructured":"Marioni RE, Shah S, McRae AF, Ritchie SJ, et al. The epigenetic clock is correlated with physical and cognitive fitness in the Lothian birth cohort 1936. Int J Epidemiol. 2015;44(4):1388\u201396.","journal-title":"International Journal of Epidemiology"},{"key":"556_CR24","doi-asserted-by":"crossref","unstructured":"Moran S, Arribas C, Esteller M. Validation of a DNA methylation microarray for 850,000 CpG sites of the human genome enriched in enhancer sequences. 2015;8(3):389\u201399 dx.\n                    doi.org\n                    \n                  .","DOI":"10.2217\/epi.15.114"},{"issue":"3","key":"556_CR25","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1093\/bioinformatics\/btt684","volume":"30","author":"TJ Morris","year":"2014","unstructured":"Morris TJ, et al. ChAMP: 450k Chip analysis methylation pipeline. Bioinformatics. 2014;30(3):428\u201330.","journal-title":"Bioinformatics"},{"issue":"1","key":"556_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/BF02289400","volume":"32","author":"MR Novick","year":"1967","unstructured":"Novick MR, Lewis C. Coefficient alpha and the reliability of composite measurements. Psychometrika. 1967;32(1):1\u201313.","journal-title":"Psychometrika"},{"issue":"7559","key":"556_CR27","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1038\/nature14465","volume":"523","author":"MD Schultz","year":"2015","unstructured":"Schultz MD, et al. Human body epigenome maps reveal noncanonical DNA methylation variation. Nature. 2015;523(7559):212\u20136.","journal-title":"Nature"},{"issue":"2","key":"556_CR28","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1093\/bioinformatics\/bts680","volume":"29","author":"AE Teschendorff","year":"2013","unstructured":"Teschendorff AE, et al. A beta-mixture quantile normalization method for correcting probe design bias in Illumina Infinium 450k DNA methylation data. Bioinformatics. 2013;29(2):189\u201396.","journal-title":"Bioinformatics"},{"issue":"3","key":"556_CR29","doi-asserted-by":"publisher","first-page":"325","DOI":"10.2217\/epi.12.21","volume":"4","author":"Nizar Touleimat","year":"2012","unstructured":"Touleimat N, Tost J. Complete pipeline for Infinium\u00ae Human Methylation 450K BeadChip data processing using subset quantile normalization for accurate DNA methylation estimation. Epigenomics. 2012;4(3):325\u201341. \n                    https:\/\/doi.org\/10.2217\/epi.12.21\n                    \n                  .","journal-title":"Epigenomics"},{"issue":"7","key":"556_CR30","doi-asserted-by":"publisher","first-page":"e90","DOI":"10.1093\/nar\/gkt090","volume":"41","author":"Timothy J. Triche","year":"2013","unstructured":"Triche TJ, Daniel J. Weisenberger D, Van Den B, Laird PW, Kimberly D. Siegmund; Low-level processing of Illumina Infinium DNA Methylation BeadArrays, Nucleic Acids Research. 201;41(7):e90. \n                    https:\/\/doi.org\/10.1093\/nar\/gkt090\n                    \n                  .","journal-title":"Nucleic Acids Research"},{"issue":"7","key":"556_CR31","doi-asserted-by":"publisher","first-page":"e90","DOI":"10.1093\/nar\/gkt090","volume":"41","author":"TJ Triche Jr","year":"2013","unstructured":"Triche TJ Jr, et al. Low-level processing of Illumina Infinium DNA Methylation BeadArrays. Nucleic Acids Res. 2013;41(7):e90.","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"556_CR32","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1093\/bioinformatics\/17.6.520","volume":"17","author":"O Troyanskaya","year":"2001","unstructured":"Troyanskaya O, et al. Missing value estimation methods for DNA microarrays. Bioinformatics. 2001;17(6):520\u20135.","journal-title":"Bioinformatics"},{"issue":"7","key":"556_CR33","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1080\/15592294.2015.1057384","volume":"10","author":"T Wang","year":"2015","unstructured":"Wang T, et al. A systematic study of normalization methods for Infinium 450K methylation data using whole-genome bisulfite sequencing data. Epigenetics. 2015;10(7):662\u20139.","journal-title":"Epigenetics"},{"issue":"2","key":"556_CR34","doi-asserted-by":"publisher","first-page":"R24","DOI":"10.1186\/gb-2014-15-2-r24","volume":"15","author":"CI Weidner","year":"2014","unstructured":"Weidner CI, et al. Aging of blood can be tracked by DNA methylation changes at just three CpG sites. Genome Biol. 2014;15(2):R24.","journal-title":"Genome Biol"},{"issue":"6","key":"556_CR35","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1038\/bjc.2013.496","volume":"109","author":"CS Wilhelm-Benartzi","year":"2013","unstructured":"Wilhelm-Benartzi CS, et al. Review of processing and analysis methods for DNA methylation array data. Br J Cancer. 2013;109(6):1394\u2013402.","journal-title":"Br J Cancer"},{"issue":"11","key":"556_CR36","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.4161\/epi.26037","volume":"8","author":"P Yousefi","year":"2014","unstructured":"Yousefi P, et al. Considerations for normalization of DNA methylation data by Illumina 450K BeadChip assay in population studies. Epigenetics. 2014;8(11):1141\u201352.","journal-title":"Epigenetics"}],"container-title":["Clinical Epigenetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13148-018-0556-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13148-018-0556-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13148-018-0556-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,14]],"date-time":"2020-05-14T10:45:21Z","timestamp":1589453121000},"score":1,"resource":{"primary":{"URL":"https:\/\/clinicalepigeneticsjournal.biomedcentral.com\/articles\/10.1186\/s13148-018-0556-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,16]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["556"],"URL":"https:\/\/doi.org\/10.1186\/s13148-018-0556-2","relation":{},"ISSN":["1868-7075","1868-7083"],"issn-type":[{"value":"1868-7075","type":"print"},{"value":"1868-7083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,16]]},"assertion":[{"value":"25 May 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 October 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 October 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Approval for the monocyte EVOIMMUNOPOP project was approved by the Ethics Committee of the Ghent University, the Ethics Board of Institut Pasteur (EVOIMMUNPOP-281297) and the relevant French Authorities (CPP, CCITRS, and CNIL). Samples were collected after written informed consent had been obtained. Approval for the DE3 study was granted from the University of British Columbia Research Ethics Board (H11-01831).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"123"}}